Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX

Hideshi Ishii; Koshi Mimori; Andrea Vecchione; Krittaya Sutheesophon; Toshiyoshi Fujiwara; Masaki Mori; Yusuke Furukawa

doi:10.1016/j.bbrc.2004.02.159

Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX

Biochem Biophys Res Commun. 2004 Apr 16;316(4):1088-93. doi: 10.1016/j.bbrc.2004.02.159.

Authors

Hideshi Ishii¹, Koshi Mimori, Andrea Vecchione, Krittaya Sutheesophon, Toshiyoshi Fujiwara, Masaki Mori, Yusuke Furukawa

Affiliation

¹ Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan. [email protected]

PMID: 15044096
DOI: 10.1016/j.bbrc.2004.02.159

Abstract

The expression of two tumor suppressor genes, fragile histidine triad (FHIT) and WW domain containing oxidoreductase (WWOX), encompassing common chromosome fragile regions, FRA3B at 3p14.2 and FRA16D at 16q23, is altered in many epithelial tumors. Since DNA sequence search shows that the FHIT gene has the E2F-1 recognition site in 5'] region, which regulates cell cycle, we tested the effect of E2F-1 overexpression in tumor cells. Ectopic E2F-1 expression led to an increase of Fhit and Wwox expression in allele remaining tumor cells and resulted in induction of apoptosis. Reporter assay showed that the E2F-1 site in FHIT 5' region was involved in the down-stream transcription after exogenous E2F-1 introduction. Chromatin immunoprecipitation detected exogenous E2F-1 binding to the recognition site in FHIT 5' region. The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acid Anhydride Hydrolases / genetics
Acid Anhydride Hydrolases / metabolism*
Cell Cycle Proteins*
Cell Line, Tumor
Chromosome Fragile Sites / genetics*
DNA-Binding Proteins*
E2F Transcription Factors
E2F1 Transcription Factor
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / metabolism*
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Oxidoreductases / genetics
Oxidoreductases / metabolism*
Recombinant Proteins / metabolism
Transcription Factors / metabolism*
Transcription Factors / pharmacology
Transcription, Genetic / genetics
Tumor Suppressor Proteins
WW Domain-Containing Oxidoreductase

Substances

Cell Cycle Proteins
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
E2F1 protein, human
Neoplasm Proteins
Recombinant Proteins
Transcription Factors
Tumor Suppressor Proteins
fragile histidine triad protein
Oxidoreductases
WW Domain-Containing Oxidoreductase
WWOX protein, human
Acid Anhydride Hydrolases